1. Field of the Invention
The present invention relates to a pharmaceutical preparation comprising L-aspartate (hereinafter "ASP") or L-asparagine (hereinafter "ASN") and a process for the preparation thereof. More particularly, the invention relates to a pharmaceutical composition of ASP or ASN for use in adding to foods, food additives, soft drinks, vitamins, an ASP compound or an ASN compound, a method of administering about 0.001-0.4 g/Kg/day of ASP or ASN to a human for preventing ethanol toxicity, and a process for the preparation of such compositions.
2. Description of Related Art
Both ASP and ASN have been obtained from natural substances or synthetic methods. It has been previously disclosed in the art that such ASP or ASN is widely used as a food additive, being added in small amounts. However, ASP or ASN is unknown to prevent ethanol toxicity by administering a large amount thereof to a human.
There have been suggestions of means for stimulating ethanol oxidation or blocking the cellular toxicity of ethanol. For example, fructose has long been suggested to have the potential to stimulate ethanol oxidation by the following mechanism: fructose is first converted to fructose 1-phosphate via the action of fructokinase with the simultaneous conversion of ATP to ADP, which is transported into the mitochondria, where it stimulates oxygen uptake and the reoxidation of NADH (Crownover et al., 1986, Scholz & Nohl 1976, Ylikari et al. 1971). But as to the efficiency of the fructose effect on ethanol oxidation, there is still dispute (Berry & Kun 1978).
In another instance, an imidazodiazepine compound R015-4513 (ethyl 8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-1][1,4]benzodiazepine-3- carboxylate) has been reported to function as a specific alcohol antagonist (Lister & Nutt 1987, Hoffman et al. 1987). The specific biochemical role of R015-4513 was noticed from its activity in reversing ethanol's stimulatory effect on GABA-mediated Cl.sup.- flux in synaptosomes (Suzdak et al. 1986). A curative effect on ethanol-induced behavioral derangements has been observed for R015-4513. However, the toxic effects of R015-4513 still limit its general application (Corda et al. 1989). In addition, GABA antagonists, serotonin uptake inhibitors, .alpha.-adrenoceptor antagonists, lithium, caffeine, Thyroid Hormone Releasing Hormone (TRH) and hyperbaric oxygen have been reported to have the potential to reverse (at least in part) some of the behavioral effects of ethanol (Lister & Nutt 1987, Judd & Huey 1984, Mezey 1976, Nuotto et al. 1982, Menon & Kodama 1985, Alkana et al. 1977, Alkana & Malcom 1982). However, most of the suggested remedies have an insignificant effect on the blood level of ethanol or on its metabolic turnover.
On the other hand, a number of reports related to liver function and alcohol metabolism are disclosed as follows. There are:
Pettersson G. (1987), "Liver alcohol dehydrogenase," CRC-Crit-Rev. 21(4) 349-89; Gianoulakis C. (1989), "The effect of alcohol on the biosynthesis and regulation of opioid peptides," Experientia 45(5), 428-35; Hoekn, J.B. et al. (1992), "Ethanol and signal transduction in the liver," FASEB - J. 6 (7) , 2386-96; Mitchell MC and Herlong HF (1986) , "Alcohol and nutrition, Caloric Value, bioenergetics and relationship to liver damage," Ann. Rev. Nutr. 6(4), 457-74; Gellert J and Teschke, R. (1988), "The biochemistry of alcohol metabolism," Z. Gastroenterol. 26 (suppl 3) 22-7; and Principles of Biochemistry (1993), (Lehninger, Nelson, Cox) 3rd ed., Chap. 18, pp. 9542-597, Worth Publishers.
U.S. Pat. No. 5,102,910 discloses a pharmaceutical composition containing (a) L-asparaginic acid, (b) L-cysteine, (c) L-glutaminic acid, (d) sodium selenate, and (e) zinc acetate or zinc sulfate for use as a liver function actuating agent. However, this patent disclosed neither a specific mechanism, nor data in vitro or in vivo.